Age-related bone loss is a major problem for the elderly. This is a multidisciplinary study of the physiology of bone metabolism in the aging population which has as its long-term goal to gain better understanding of the etiology and to develop better ways to prevent and treat age-related bone loss. Project 1 ("Pathophysiology of Types of Age-Related Bone Loss") will seek to characterize the pathophysiology and etiology of involutional osteoporosis and will be based on intensive studies of control and osteoporotic subjects in the Mayo General Clinical Research Center. Project 2 ("Risk Factors for Hip Fracture Among the Elderly") consists of a series of large epidemiologic retrospective cohort studies which will attempt to identify common etiologic factors among patients with specific disease and surgical procedures which have been shown in preliminary studies to contribute substantially to the development of hip fractures among the elderly. Based on these findings, testable hypotheses of pathogenesis will be developed. Project 3 ("Noncollagenous Bone Matrix Proteins") will seek to identify and characterize bone specific proteins in the noncollagenous component of bone matrix which could have important roles in maintaining bone structure and/or in regulating bone cell function. The effect of aging on the bone content of these proteins will also be examined. Project 4 ("Immunochemical Quantitation of Bone Specific Proteins") will seek to develop monoclonal and polyclonal radioimmunoassay systems for measurement of the bone specific proteins. These will be validated by comparison with existing methodologies including bone histomorphometry and radiocalcium kinetic studies in normal subjects and subjects with bone losing diseases. These markers will be crucial for implementing studies on bone metabolism that involve large numbers of elderly subjects who, because of the infirmities of age, are poor candidates for bone biopsy, radiocalcium kinetic, and calcium balance studies. An administrative and biostatistical core unit will provide the statistical support required to carry out the four projects as well as some other general support items.